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Orthostatic Intolerance and Motion Sickness after Parabolic Flight 

Todd T. Schlegel', Troy E. Brown", Scott J. Wood\ Edgar W. Benavides", Roberta L. 
Bondar\ Flo Stein^ Peyman Moradshahi\ Deborah L. Harm' and Phillip A. Low" 

I Life Sciences Research Laboratories. National Aeronautics and Space Administration, 
Johnson Space Center and^Wyle Laboratories. Houston. Texas, 77058; ^ Baylor College 
of Medicine, Houston, Texas, 77030; -^Ryerson Polytechnic University, Toronto, Ontario, 
Canada, MSB 2K3; ^Maple Lake Non-Invasive Laboratory, Farmington, New Mexico, 
87109; and ^Autonomic Reflex Laboratory, Mayo Foundation, Rochester, Minnesota. 


Address Correspondence to: 
Todd T. Schlegel, MD 
NASA Johnson Space Center 
Mail Code SD3 
Houston, Texas 77058 

Phone: 281-483-9643 
Fax: 281-244-5734 

Schlegel et al.. Orthostatic Intolerance After Parabolic Flight 

Orthostatic intolerance is common in astronauts after prolonged space flight. However, 
the "push-pull effect" in military aviators suggests that brief exposures to transitions 
between hypo- and hypergravity are sufficient to induce untoward autonomic 
cardiovascular physiology in susceptible individuals. We therefore investigated 
orthostatic tolerance and autonomic cardiovascular function in 16 healthy test subjects 
before and after a seated 2-hr parabolic flight. At the same time, we also investigated 
relationships between parabolic flight-induced vomiting and changes in orthostatic and 
autonomic cardiovascular function. After parabolic flight, 8 of 16 subjects could not 
tolerate a 30-min upright tilt test, compared to 2 of 16 before flight. Whereas new 
intolerance in non-Vomiters resembled the clinical postural tachycardia syndrome 
(POTS), new intolerance in Vomiters was characterized by comparatively isolated 
upright hypocapnia and cerebral vasoconstriction. As a group, Vomiters also had 
evidence for increased postflight fluctuations in efferent vagal-cardiac nerve traffic 
occurring independently of any superimposed change in respiration. Results suggest that 
syndromes of orthostatic intolerance resembling those occurring after space flight can 
occur after a brief (i.e., 2-hr) parabolic flight. 

Key Words: postural tachycardia syndrome (POTS), microgravity, hypergravity, 
vomiting, autonomic, space flight 

Schlegel et al.. Orthostatic Intolerance After Parabolic Flight 1 

ORTHOSTATIC INTOLERANCE is common in astronauts after prolonged exposure to 
microgravity (6, 14). However, the existence of the so-called "push-pull effect" in 
military aviators — i.e., the heightened risk, in many high-performance pilots, of G- 
induced loss of consciousness during an extreme +G flight-maneuver in the z direction 
(+GJ if a -G3 flight-maneuver has just been completed (1, 30) — suggests that untoward 
autonomic cardiovascular physiology can be generated very rapidly under the right 
gravitational conditions. This rapidity is potentially confirmed by our own observation 
that many individuals who have just experienced even lesser extremes of hypo- and 
hypergravity during brief parabolic flights also develop lightheadedness that can persist 
after landing. One of the principal goals of this study, therefore, was to take advantage of 
the relatively short duration of parabolic flights (compared to space flights) to investigate 
the possibility that exposure to acute gravitational transitions alone might be sufficient to 
induce untoward autonomic cardiovascular physiology and to reduce orthostatic tolerance 
in susceptible individuals after landing. 

Motion sickness is another common condition affecting both returning astronauts 
(44) and individuals returning from parabolic flight (25). To our knowledge, however, a 
prospective investigation of changes in orthostatic tolerance in individuals recovering 
from motion sickness has never been performed. Recently, Buckey et al. (6) have 
described a form of post-space flight orthostatic intolerance in two returning astronauts, 
possibly related to motion sickness, that was not characterized by any clear hypotensive 
event. A second, related goal of this study, therefore, was to utilize the inevitable motion 
sickness generated in susceptible individuals during and after parabolic flights to 

Schlegel et al, Orthostatic Intolerance After Parabolic Flight 2 

investigate relationships between motion sickness and concomitant changes, if any, in 
autonomic cardiovascular and orthostatic function. 

Our specific hypotheses were that: 7) autonomic cardiovascular dysfunction and 
orthostatic intolerance do indeed occur with an increased frequency after a standard 2-hr 
parabolic flight; but that 2) the type and/or degree of autonomic cardiovascular 
dysfunction and orthostatic intolerance necessarily differs in individuals who have and 
who have not vomited as a result of parabolic flight. 


Subjects. Sixteen healthy test subjects (ten men and six non-pregnant women, 
mean age 32 years, range 22-45 years) participated in the study, which was approved by 
the Johnson Space Center Institutional Review Board. All subjects were free of 
cardiopulmonary, renal or other systemic disease, and each gave written, informed 
consent after passing an U.S. Air Force Class III physical examination. In addition, all 
subjects were nonsmokers who had normal blood pressure (BP), hemoglobin/hematocrit, 
creatinine, electrolytes, liver function tests and urinalyses (including drug screens). 
Caffeine, alcohol, heavy exercise, anti-motion sickness medications and all other 
medications were strictly prohibited beginning 24 hours prior to any testing, which was 
commenced in the morning hours after a low-fat breakfast. 

Parabolic flights and motion sickness scores. While loosely restrained at the 
waist, subjects flew four sets often parabolas in the seated position aboard NASA's KC- 
135 aircraft, a Boeing 707 specifically modified for parabolic flight. During their flights, 
subjects were instructed to avoid unnecessary head movements and to look forward at a 

Schlegel et al., Orthostatic Intolerance After Parabolic Flight 3 

computer monitor placed immediately in front of them. As verified by an accelerometer 
mounted inside the aircraft, single parabolas consisted of the following three phases, each 
lasting approximately 20-25 s: 7) "pull-up" with increased G-load of up to +1.8 G,; 2) 
microgravity (approximately 0.01 GJ; and 3) "pull-out" with increased G-load of up to 
+ 1.8G^ (see ref. 48). During the entire inflight and postflight periods, motion sickness 
scores were estimated and recorded for each subject at 5 min intervals using Graybiel's 
standard 16-point scale (16). These scores were reduced (for simplification) to the 
maximum spot score attained during the entire protocol and the maximum spot score 
attained during postflight tilt testing approximately 40-70 min after landing. For 
statistical analyses, the maximum spot score overall was also used to separate subjects 
into two principal groups: Vomiters (maximum spot Graybiel score > 16) and non- 
Vomiters (maximum spot Graybiel score < 16). 

Cardiovascular and cerebrovascular measurements. Cardiovascular data were 
collected during identical pre- and postflight sessions in the supine and tilted-upright 
positions in a hangar facility at Ellington Air Field, Pasadena, TX. The preflight session 
occurred 1-5 days prior to parabolic flight and the postflight session immediately after 
parabolic flight. Prior to testing, subjects were first instrumented with 1) 
electrocardiographic leads and electrodes (including an electrode for impedance 
measurements of abdominal-muscle respiratory excursions, Physio-Control, Redmond, 
WA); 2) impedance cardiographic leads and electrodes (BoMed, Irvine, CA); and 3) a 
finger photoplethysmographic device (Finapres 2300, Ohmeda, Englewood, CO) for beat- 
to-beat estimates of BP. The continuous cardiovascular signals from these devices were 
digitally recorded and integrated by using a special software program (28, 48) that 

Schlegel et al., Orthostatic Intolerance After Parabolic Flight 4 

automatically entrains beat-to-beat heart rate (HR), stroke volume (SV) and mean BP 
(MBP) to create a real-time pictorial representation for beat-to-beat cardiac output [(CO) 
= HR X SV)] and total peripheral resistance [(TPR) = MBP/CO]. Throughout supine and 
upright testing, end-tidal COj was also measured via a nasal probe (Puritan-Bennett, 
Wilmington, MA) while a 2 MHz flat ultrasound probe (TRANSPECT, Medasonics, 
Mountain View, CA) was mounted over the right temporal bone to obtain transcranial 
Doppler (TCD) recordings of blood flow velocities through the right middle cerebral 
artery. The principal TCD indices derived for the present study were the middle cerebral 
artery mean flow velocity (MCA-MFV) and the estimated cerebral vascular resistance 
(CVR,„), which is the estimated MBP at the level of the circle of Willis divided by the 
MCA-MFV (14). In certain representative subjects, to allow for a very detailed 
characterization of pre- to postflight changes in cardiovascular function in the context of 
upright tilt, we simply plotted the continuous trends for the TCD parameters alongside of 
simultaneous continuous trends for MBP, HR, SV, TPR and end-tidal COj (see Figs. 1- 
4). While some error may be associated with the use of impedance cardiography for 
measurements of beat-to-beat SV, finger photoplethysmography for measurements of 
beat-to-beat BP, and TCD for measurements of beat-to-beat MCA-MFV, the combined 
techniques are nonetheless considered reliable for studying changes in cardiovascular 
function during upright tilt (40). 

Both pre- and postflight, the specific sequential activities of test subjects were as 
follows: 1) ambulation to the testing area; 2) instrumentation (as noted above); i) supine 
rest for 15 min; 4) supine controlled breathing at 0.25 Hz for 5 min, or until 256 
consecutive heart beats and beat-to-beat arterial pressures were recorded for subsequent 

Schlegel et al., Orthostatic Intolerance After Parabolic Flight 5 

spectral analyses; 5) supine carotid-cardiac baroreflex testing; 6) supine Valsalva 
maneuver testing; 7) 3-5 min of additional supine rest; and, finally 8) upright tilt testing. 
The majority of these activities are described in greater detail below. On the aircraft 
itself, both immediately before and after flight, subjects also performed Valsalva tests in 
the seated position. These seated tests complemented our earlier investigation (in the 
same subjects) of seated responses to Valsalva maneuvers during the inflight period (48). 

Tilt tests. After supine autonomic testing both pre- and postflight, subjects were 
secured and pitched acutely (within 10-12 s) into the 80-degree head-up position by using 
a standard clinical autonomic tilt table (Tri W-G, Valley City, ND). A right arm- 
extension attached to the table was used during tilt to maintain the Finapres finger cuff at 
the level of the heart. Once obtained, the 80-degree head-up position was sustained for 
30 min or until presyncopal vital signs and/or symptoms ensued. During min 1-10 of the 
upright position both pre- and postflight, some subjects also performed controlled 
breathing at 0.25 Hz for a total of 5 min (e.g., see Fig. 2). 

In addition to the continuous cardiovascular and cerebrovascular measurements 
noted above, manual recordings of systolic and diastolic BP (SBP and DBF, respectively) 
were also obtained on a minute-to-minute basis before, during and after tilt via a 
sphygmomanometer attached to the non-extended (left) arm. During tilt, these recordings 
were increased to every 30 s upon the onset of new symptoms, TCD changes, or a marked 
decrease in BP or HR. For analyses, the manual BP recordings were averaged for each 
individual according to three epochs: epoch 1, the average of the two minute-to-minute 
BP recordings in the supine position immediately preceding upright tilt; epoch 2, the 
average of all BP recordings from minutes 1-10 of upright tiU or portion thereof 

Schlegel et al., Orthostatic Intolerance After Parabolic Flight 6 

(excluding any data collected during controlled breathing or during the minute 
immediately prior to orthostatic failure, if failure occurred during this epoch); and, epoch 
3, the average of one or more BP recordings from the last minute of upright tilt. The 
epochal averages for SBP, DBF and MB? from individual subjects were then used to 
derive corresponding averages for groups of subjects (i.e., whole group, Vomiters, non- 
Vomiters). A similar procedure was also performed for pulse pressure [(PP) = SBP- 
DBP], HR, SV, CO, TPR (derived from the manual measurements of MBP), end-tidal 
CO2 and the TCD parameters. In one subject, the preflight TCD signal was corrupted 
such that it was not possible to calculate averages for MCA-MFV and CVR,„ over any 
given epoch. In another subject, the averages for MCA-MFV and CVR,,, during epoch 1 
had to be obtained from a slightly earlier period in the supine position both pre- and 
postflight because of intermittent electrical interference in the preflight TCD signal. 

Derivation of power spectra. Spectral powers for the supine position were 
derived from the 5-min series of consecutive R-R intervals, SBPs and DBFs collected 
during metronome-controlled breathing (5) at 0.25 Hz both pre- and postflight. Prior to 
preflight testing, subjects first chose a comfortable respiratory excursion (tidal volume) 
and practiced breathing to the metronome at that excursion. They were then asked to use 
this same excursion throughout all subsequent pre- and postflight tests involving 
controlled frequency breathing. During data collection itself, based upon our observation 
of end-tidal CO2 levels and of abdominal and nasal respiratory movements and tracings, 
we also provided verbal feedback to the subjects as necessary to ensure that they were 
maintaining gross consistency in respiration. 

Schlegel et al., Orthostatic Intolerance After Parabolic Flight 7 

For spectral analyses, the Welch algorithm for averaging periodograms (54) was 
used in accordance with the method of Rabiner et al. (42). Specifically, the continuous 
series of R-R intervals, SBPs or DBFs was fitted to a cubic spline function, interpolated 
at 8 Hz to obtain equidistant time intervals, and divided into seven equal overlapping 
segments. Segments were then de-trended, Hanning window filtered, fast-Fourier 
transformed, and averaged to produce the spectrum estimate. Spectral power was 
integrated over three defined frequency bandwidths: "low" frequencies between 0.05 and 
0.15 Hz; "high" (or respiratory) frequencies between 0.20 and 0.30 Hz; and all 
frequencies (i.e., "total power") below 0.50 Hz (24). We also calculated a 
"sympatho vagal index", defined as the ratio of the low frequency power of SEP to the 
high frequency power of R-R intervals. This index resembles (but is not identical to) the 
sympathovagal index recently proposed by Novak et al, (39). 

Carotid-cardiac baroreflex responsiveness. Both pre- and postflight, supine 
caroUd-cardiac baroreflex responsiveness was measured in subjects via pressure changes 
applied to a tightly-sealing silastic neck chamber connected to a computer-controlled 
bellows (E-2000 Neck Baro Reflex System, Engineering Development Laboratories, 
Newport News, VA) (52). During held expiration, neck chamber pressure was raised to 
+40 mmHg, reduced to -60 mmHg, again raised to +40 mmHg, and then released, all in 
consecutive R-wave-triggered steps of +20 mmHg. This sequence was then repeated 
seven times and the responses averaged for each test subject. R-R interval responses to 
carotid baroreceptor stimulation, defined as carotid distending pressure (SBP minus neck 
pressure), were reduced to the maximum slope of the stimulus-response relation, the 
maximum range of R-R interval responses, and the operational point (11, 12). Maximum 

Schlegel et al., Orthostatic Intolerance After Parabolic Flight 8 

slopes were identified witli linear regression analyses applied to each set of three 
consecutive data pairs on the stimulus-response relation. Operational point, a measure of 
the amount of buffering capacity below baseline systolic pressure, was calculated as: [(R- 
R interval at mmHg neck pressure minus minimum R-R interval)/R-R interval range] X 

Although past studies of the carotid-cardiac baroreflex have concentrated on the 
response to a hypotensive stimulus train (+40 mmHg to -60 mmHg), we also measured 
the response to a hypertensive stimulus train (-60 mmHg to +40 mmHg) to explore the 
hysteresis of the system. 

Valsalva measurements. Valsalva maneuvers were completed at an expiratory 
pressure of 30 mmHg for 15 s as previously described (48). Prior to the strains, which 
were performed in triplicate, subjects first had at least 15 min of rest in the assigned 
postural configuration (i.e., supine or seated). Each strain was also preceded and 
followed by at least 1 min of controlled frequency breathing at 0.25 Hz. To produce the 
strains, subjects blew into a mouthpiece connected by short plastic tube to a calibrated 
pressure gauge while the electrocardiogram, impedance cardiogram, and arterial and 
expiratory pressures were continuously recorded. 

Because responses during phases 1 and III of Valsalva maneuvers are believed to 
reflect mostly mechanical changes (3, 46), we focused our analyses on variations in MBP 
during the "autonomic" Valsalva phases II and IV. Changes in MBP during phases II and 
IV were specifically calculated as follows: I) A early-phase II (phase IIJ was the change 
in MBP occurring between the maximal MBP value during phase I and the minimal MBP 

Schlegel et al., Orthostatic Intolerance After Parabolic Flight 9 

value during phase II,; 2) A late-phase II (phase II,) was the change in MBP occurring 
between the minimal MBP value during phase II, and the maximal MBP value during 
phase 11,; and 3) A phase IV was the change in MBP occurring between the minimal MBP 
value during phase III and the maximal MBP value during phase IV. In addition to the 
absolute changes in MBP, we also calculated the temporal duration of changes in the 
MBP response during Valsalva phases II, and II, (see ref. 48). During the immediate 
postflight period in the aircraft, one subject was not able to perform seated Valsalva 
maneuvers because of severe motion sickness. 

Statistics. All results are reported as means + SE with the exception of the 
Valsalva-related results, which are reported as means + SD to facilitate comparison with 
our previously-published Valsalva-related results from the inflight period (48). Because 
normality was often violated, we used non-parametric statistics for all comparisons. 
Specifically, we used the Wilcoxon signed-rank test for within-group comparisons (i.e., 
before vs. after parabolic flight) and the Mann- Whitney rank sum test for between-group 
comparisons (i.e., Vomiters vs. non-Vomiters) (15). For all statistical determinations, 
significance was accepted at P < 0.05. 


Overall responses to upright tilt. Nearly all subjects had cardiovascular changes 
postflight that were indicative of decreased orthostatic tolerance. Table 1 , for example, 
shows pre- to postflight changes in supine and upright cardiovascular data for the entire 
group. In the supine position postflight compared to preflight, the group as a whole had 

Schlegel et al., Orthostatic Intolerance After Parabolic Flight 10 

decreased DBP, MBP and TPR and increased SV and CO. During min 1-10 of the 
upright position (or portion thereof) postflight compared to preflight, the group as a 
whole had decreased SEP, TPR and MCA-MFV and increased CO. Finally, during the 
last minute of upright tilt postflight compared to preflight, the group as a whole had 
decreased DBP, MBP, TPR, MCA-MFV and end-tidal CO2 and increased HR and CO. 
The decreased end-tidal CO2 during the last minute of upright tilt postflight was not 
related to any change in the natural respiratory rate (i.e., 3.7 ± 0.2 breaths/min postflight 
vs. 3.7 ± 0.2 breaths/min preflight; P > 0.05). 

Individual subject characteristics. Table 2 outlines the susceptibility of 
individual subjects to both motion sickness and orthostatic intolerance. Six of the 16 
subjects vomited as a result of parabolic flight (shaded background) whereas ten did not. 
In addition, eight subjects — five of the six Vomiters and three of the ten non-Vomiters — 
had frank orthostatic intolerance postflight, defined as an inability to complete the 30-min 
postflight upright tilt test without limiting signs or symptoms. Two of the female 
Vomiters, however (subjects #15 and #16), were also the only subjects who had frank 
orthostatic intolerance preflight. In these two subjects, the specific mode of orthostatic 
failure was typical vasovagal presyncope (33) both pre- and postflight. The varying 
modes of orthostatic failure noted in the six subjects who were frankly intolerant only to 
postflight upright tilt are outlined as case studies below. 

Tilt-related case studies: 

A. Intolerant non-Vomiters. Although all ten non-Vomiters were tolerant to 
upright tilt before flight, three had frank orthostatic intolerance after flight. Importantly, 
all three of these subjects had scores of zero on the Graybiel motion sickness scale 

Schlegel et al., Orthostatic Intolerance After Parabolic Flight 1 1 

throughout postflight cardiovascular testing, with two of the three being completely 
resistant to motion sickness at all times (Table 2). Figure 1 shows the continuous 
preflight (light tracing) and postflight (dark tracing) responses to upright tilt of one of 
these three subjects (#7, Table 2). Postflight, one of the most remarkable changes was the 
subject's postural tachycardia, which developed in conjunction with several other signs 
and symptoms (see the Fig. 1 legend). A second non-Vomiter who developed frank 
orthostatic intolerance postflight (subject #4, Table 2) had similar pre- to postflight 
changes in overall upright physiology. The principal difference was that subject #4 also 
had intermittent episodes of upright hypotension. Postflight, the responses to upright tilt 
of both subject #7 and subject #4 fulfilled diagnostic criteria for the clinical postural 
tachycardia syndrome (POTS) (27, 38, 39, 47, 49, 50). 

Figure 2 shows corresponding pre- and postflight data from the final non-Vomiter 
who was intolerant to tilt only after flight (subject #5, Table 2). Although this subject 
also had POTS-like physiology postflight, she was distinguished from subjects #4 and #7 
by having 1) more instantaneous cardioacceleration, hypocapnia and cerebral 
vasoconstriction (relative to preflight) at the onset of her postflight upright tilt; 2) more 
abrupt cardiovascular and cerebrovascular changes (specifically, a vasovagal-like 
episode) (17, 33) at the termination of her postflight upright tilt; and 3) a greater 
difference between postflight SV and preflight SV throughout the upright period. This 
subject was also distinguished from the two Vomiters who had vasovagal episodes both 
pre- and postflight in that her postflight presyncope was heralded by a much more 
significant postural tachycardia relative to preflight. 

Schlegel et al., Orthostatic Intolerance After Parabolic Flight 12 

B. Intolerant Vomiters. Three of the four Vomiters who were tolerant to upright 
tilt before flight developed frank orthostatic intolerance after flight (subjects #12, #13 and 
#14, Table 2). However, none of these individuals had absolute hypotension (SBP < 90) 
at the end of postflight upright tilt. Instead, all three had other signs and/or symptoms 
that warranted early tilt-test termination. Figure 3 shows an expanded portion of strictly 
postflight upright tilt data from one of these subjects (#13, Table 2). Shortly after 
landing, this subject's severe in-flight motion sickness had essentially resolved such that 
she was asymptomatic for the first 1 1 min of postflight upright tilt. However, near 
postflight upright min 1 1 , the subject redeveloped mild nausea which progressed (without 
much warning) to frank retching and vomiting at postflight upright min 12.5. Of 
particular interest were the decrease in end-tidal COj, decrease in MCA-MFV and 
increase in CVR^^jthat developed concomitantly with the subject's prodromal nausea (not 
vomiting) at minutes 11-12.5 of the postflight tilt test. Consistent with the abrupt 
cerebral vasoconstriction, the subject also suffered from moderate lightheadedness at the 
time of her upright nausea. Of the other two Vomiters who completed uneventful 
preflight (but not postflight) tilt tests, one (subject #14, Table 2) had a postflight pattern 
very similar to that of subject #13 whereas the other (subject #12, Table 2) did not 
develop postflight upright nausea. Instead, subject #12 developed isolated (and limiting) 
lightheadedness after only 4 min of postflight upright tilt along with abrupt changes in 
end-tidal CO,, MCA-MFV and CVR^^, resembling those shown in Fig. 3. Because we 
know of no existing nomenclature for these nonhypotensive forms of orthostatic 
intolerance occurring in motion sick subjects, we have termed them "prostration 
intolerance" for the purposes of this paper. 

Schlegel et al., Orthostatic Intolerance After Parabolic Flight 13 

Tolerant vs. intolerant subjects. As partially evidenced by data from the entire 
group (Table 1), postflight deficits in orthostatic tolerance such as exaggerated upright 
cardioacceleration and hypocapnia also occurred in so-called "tolerant" subjects. A 
specific case study is illustrated in Figure 4. 

Tilt-related factors postflight that clearly distinguished tolerant subjects from 
frankly intolerant subjects are shown in Figure 5. Postflight, compared to the eight 
tolerant subjects, the eight frankly intolerant subjects had: 1) decreased TPR in the supine 
position; 2) decreased rather than increased TPR during the transition from the early 
portion of upright tilt (i.e., min 1-10 or portion thereof) to the end of upright tilt; and 3) 
decreased TPR, SBP, and PP at the end of upright tilt. 

Spectral power of supine R-R intervals and arterial pressures. Pre- to postflight 
changes in supine R-R interval and arterial pressure spectral powers for the entire group 
and for Vomiters vs. non-Vomiters are shown in Table 3. For the group as a whole, none 
of the R-R interval spectral parameters changed significantly from pre- to post-parabolic 
flight, nor did the sympathovagal index. However, the total power of arterial pressures 
increased in the group as a whole after flight (SBP, P < 0.05; DBP, P < 0.01). 

After parabolic flight, the high frequency and total power of R-R intervals 
increased in Vomiters {P < 0.05 for total power only) but decreased (non-significantly) in 
non-Vomiters, leading to significant between-groups differences in these parameters. In 
addition, Vomiters had no changes in their arterial pressure spectral powers postflight 
whereas non-Vomiters, like the group as a whole, had increases in the total power of both 
SBP {P < 0.05) and DBP (P < 0.01). The non-significant decrease in the low frequency 

Schlegel et al, Orthostatic Intolerance After Parabolic Flight 14 

power of SBP in Vomiters, and the non-significant increase in non-Vomiters, translated 
into a significant between-groups difference in this parameter postflight {P < 0.05). 
Sympathovagal index followed the same general pattern, with the difference between 
Vomiters and non-Vomiters reaching a similar level of significance postflight (P < 0.05). 

The power spectral results might be summarized as follows: the Vomiter group 
tended to respond to parabolic flight with enhanced R-R interval variability whereas the 
non-Vomiter group tended to respond to parabolic flight with enhanced arterial pressure 
variability, primarily in the low frequency region. 

Carotid-cardiac baroreflex responses. For the group as a whole, parabolic flight 
did not affect the maximum slope, range or operational point of the carotid-cardiac 
baroreflex. This was true for both the hypo- and hypertensive stimulus trains. However, 
postflight compared to preflight, during the hypotensive stimulus train, Vomiters had a 
significant increase in maximum slope (3.7 + 0.6 vs. 2.4 + 0.7 ms/mmHg, P = 0.03), a 
nearly significant increase in range (204 + 31 vs. 153 + 40 ms, P = 0.06), and no change 
in operational percent whereas non-Vomiters had no changes in any of these parameters. 

Valsalva responses. Table 4 shows the pre- and postflight Valsalva responses of 
the whole group and of Vomiters vs. non-Vomiters. Postflight, in the seated (but not in 
the supine) position, the absolute MB? responses of the whole group and of Vomiters 
became significantly attenuated during Valsalva phases 11^ and II, (P < 0.05), whereas the 
absolute MBP responses of non-Vomiters were unchanged. In addition, the temporal 
duration of seated Valsalva phase 11^ increased postflight in Vomiters (P < 0.05) but 

Schlegel et at., Orthostatic Intolerance After Parabolic Flight 15 

decreased (non-significantly) in non-Vomiters, leading to a significant postflight 
between-groups difference in this parameter (P = 0.02). 

Tolerant vs. intolerant non-Vomiters. Finally, because autonomic cardiovasular 
function was independently influenced by the presence of recent vomiting (Tables 3-4 
and the baroreflex results above), we also analyzed postflight differences in supine 
autonomic cardiovascular function between non-Vomiters who were tolerant vs. frankly 
intolerant to postflight upright tilt (Figure 6). Compared to the seven non-Vomiters who 
were tolerant to postflight upright tilt, the three non-Vomiters who who were frankly 
intolerant had: 7) greater percentage increases in the low frequency power of SBP and 
DBP from pre- to postflight {P < 0.05 for each); 2) greater percentage increases in the 
sympathovagal index from pre- to postflight (P < 0.05); 3) greater percentage increases in 
the absolute MBP response during supine Valsalva phase 11, from pre- to postflight (P < 
0.05); and 4) a trend toward decreases (rather than increases) in the range (P = 0.07) and 
maximum slope (P = 0.07) of the hypotensive carotid-cardiac baroreflex from pre-to- 


Our results indicate that exposures to short, repetitive gravitational transitions 
alone are sufficient to reduce orthostatic tolerance in susceptible individuals. This 
conclusion is supported not only by the fourfold increase in the number of subjects who 
developed frank orthostatic intolerance after (compared to before) parabolic flight, but 
also by the subtle postflight deficits in orthostatic tolerance that occurred in nearly all 

Schlegel et al., Orthostatic Intolerance After Parabolic Flight 1 6 

individuals (Table 1, Fig. 4). Our data also indicate that subjects who have and who have 
not vomited as a result of parabolic flight develop differing syndromes of orthostatic 
intolerance as well as differing directional changes in autonomic cardiovascular function 
after flight. These differences are discussed in detail below. 

Post/light reductions in orthostatic tolerance. After parabolic flight, frank 
orthostatic intolerance that was not present before flight took one of two general forms 
(Table 2): POTS-like intolerance (e.g.. Figs. 1-2) and prostration intolerance (e.g.. Fig. 3). 
POTS-like intolerance occurred only in non-Vomiters, whereas prostration intolerance 
occurred only in Vomiters. In the upright position postflight compared to preflight, both 
of these general forms of intolerance were characterize* by relative hypocapnia and 
cerebral vasoconstriction. However, whereas notable postural tachycardia and either 
absolute hypertension or hypotension characterized POTS-like intolerance, these events 
did not typically characterize prostration intolerance. 

POTS-like intolerance. A failure of the upright TPR response characterized 
POTS-like intolerance in this study (Figs. 1-2) and also characterizes the orthostatic 
intolerance of both returning astronauts (6, 14) and of patients with POTS who are prone 
to presyncope (47). Nonetheless, the occurrence of POTS-like intolerance after parabolic 
flight is surprising for at least two reasons. First, although clinical POTS is considered a 
model for abnormal cardiovascular function after space flight (27, 45, 50), parabolic 
flight does not involve prolonged exposures to microgravity, but only short, repetitive 
exposures to both micro- and hypergravity. Therefore, factors such as sustained cephalad 
fluid-shifting and disuse of baroreceptors cannot explain post-parabolic flight POTS. 
Other etiologies must be sought. Second, in the present study, all three of the individuals 

Schlegel et al., Orthostatic Intolerance After Parabolic Flight 17 

who developed postflight POTS were resistant to motion sicicness, with two of the three 
being completely resistant at all times (Table 2). Therefore, the postflight signs/symptoms 
of these subjects also cannot be explained on the basis of sickness-related factors such as 
nausea, fluid loss, etc. 

One of the subjects who developed POTS after parabolic flight had upright 
hypertension rather than hypotension (Fig. 1). In the setting of clinical POTS, upright 
hypertension is especially suggestive of dysautonomia originating in the brainstem (27). 
Interestingly, signals from the otolith organs are known to modulate brainstem autonomic 
pathways involved in the control of the sympathetic nervous system (55, 56), and both 
astronauts and parabolic flyers receive novel inputs from these organs (i.e., prolonged 
otolith destimulation and repetitive otolith stimulation/destimulation, respectively). 
Therefore, it seems possible that altered otolith function could contribute to a transient 
central dysautonomia in susceptible individuals after either space flight or parabolic flight 
(55). Although both types of flight also undoubtedly directly influence other 
gravireceptors and baroreceptors, Colehour and Graybiel (7) have nonetheless 
demonstrated that unlike healthy subjects, individuals with bilateral labyrinthine 
deficiency do not have increases in their urinary excretion of norepinephrine immediately 
after an acrobatic flight stress. More recently, Jian et al. (21) have also demonstrated that 
cats with bilateral vestibular lesions can develop either orthostatic hypotension (i.e., in 
accord with the findings of others (9)) or, alternatively, orthostatic hypertension. 

Prostration intolerance. The prostration form of orthostatic intolerance 
experienced by three of our motion sick subjects after parabolic flight might provide an 
explanation for the non-hypotensive form of orthostatic intolerance recently noted by 

Schlegel et al., Orthostatic Intolerance After Parabolic Flight 18 

Buckey et al. (6) in two returning astronauts. Specifically, whereas end-tidal COj and 
MCA-MFV were not measured in the astronaut study, in the present study, end-tidal CO2 
and MCA-MFV were always decreasing (and CVR^^, was always increasing) in motion 
sick-susceptible subjects at the time of their most severe upright symptoms (e.g., Fig. 3). 
The fact that acute hypocapnia accompanied cerebral vasoconstriction in our upright 
motion sick subjects suggests that alterations in upright respiratory activity may be 
partially responsible for the lightheadedness of these individuals. The notion that acute 
hypocapnia alone is able to elicit lightheadedness, cerebral hypoperfusion and early 
presyncope in patients prone to orthostatic intolerance has recently been demonstrated 
conclusively by Novak et al. (40). However, in their patients, exaggerated hypocapnia 
during upright tilt was attributed to a compensatory respiratory response to inadequate 
peripheral vasoconstriction (40). On the other hand, in our motion sick subjects, the 
corresponding hypocapnia cannot reflect such compensation since it usually occurred 
before (or even outside of the context of) any overt failure of systemic vasoconstriction 
(e.g., Fig. 3). One possibility is that when nausea progresses during the development of 
motion sickness, it simply induces anxiety and therefore acute hyperventilation. 
However, inasmuch as motion sickness requires the presence of a functioning vestibular 
apparatus for induction (31), acute hyperventilation in motion sick subjects could also be 
driven by a change in supine -to-upright vestibulo-respiratory regulation (56) (i.e., by a 
brainstem-mediated as opposed to a cerebral hemisphere-mediated phenomenon). Yet 
another possibility (presently unproven) is that vestibulo-autonomic pathways — 
particularly those that travel via the cerebellum (29, 43) — might also have a more direct 
effect on cerebrovascular autoregulation in the context of motion sickness. 

Schlegel et al, Orthostatic Intolerance After Parabolic Flight 19 

Hypocapnia and cerebral hypoperfusion. The changes in end-tidal CO2 in our 
overall group postflight (Table 1) support another recent finding of Novak et al. (40); 
namely, that individuals who are prone to presyncope only develop significant 
hypocapnia (relative to healthy subjects) after assumption of the upright position. As in 
Novak et al.'s patients, exaggerated upright hypocapnia in this study (i.e., postflight) was 
also not due to any significant increase in the average upright respiratory rate. It may not 
necessarily follow, however, that exaggerated upright hypocapnia is therefore strictly 
attributable to a hyperventilation resulting from an increase in the average upright tidal 
volume (40). As an example, even though end-tidal COj levels are often significantly 
decreased in healthy subjects after movement to the upright position (4, 41, 51), some 
investigators have noted concomitant increases in tidal volume and alveolar minute 
ventilation (41) whereas some have not (4, 23, 51), In addition, end-tidal CO2 levels do 
not necessarily reflect arterial CO2 levels in a consistent fashion across all postural 
conditions inasmuch as ventilation/perfusion mismatches and pulmonary dead space are 
relatively increased in the upright position (41). 

Serrador et al. (51) have recently suggested that supine-to-upright decreases in 
end-tidal COj in healthy subjects may reflect redistribution of blood and tissue CO, stores 
rather than changes in minute ventilation, alveolar ventilation, dead space, cardiac output 
or CO2 production. If so, such redistribution could potentially explain some of the 
variable patterns of exaggerated upright hypocapnia that we noted postflight. Our subject 
#5, for example (Fig. 2), was unique in that she had a very early post- vs. preflight 
difference in upright end-tidal CO, that persisted in the face of grossly-equivalent 
controlled breathing from pre- to postflight (see especially the stippled area. Fig. 2). 

Schlegel et al, Orthostatic Intolerance After Parabolic Flight 20 

Thus, at least during the early portions of postflight upright tiU, subject #5's relative 
hypocapnia was probably not due to hyperventilation, but rather to some other etiology, 
possibly CO2 redistribution (51). On the other hand, like nearly all of the subjects who 
became presyncopal after flight, subject #5 also began to breathe more irregularly in the 
upright position as her overall condition worsened, presumably in an attempt to increase 
venous return and to activate other compensatory autonomic reflexes (40). Thus, 
hyperventilation probably contributed to the superimposed hypocapnia that began 
abruptly near min 22 of her postflight upright tilt test — i.e., just prior to her actual 
vasovagal event (Fig. 2). Rather than immediate upright hyperventilation, a greater initial 
venous redistribution of CO, in subject #5 might also be consistent with the exaggerated 
falls in central venous pressure that are known to occur at the onset of upright tilt in 
groups of healthy subjects who are ultimately prone to vasovagal presyncope (34). 

Changes in autonomic cardiovascular function: 

A. Vomiters. At least three findings from this study suggest that fluctuations in 
efferent vagal-cardiac nerve traffic are intrinsically heightened in the minutes after 
emesis. First, in the supine position postflight compared to preflight, Vomiters had 
increases in the total spectral power of R-R intervals (Table 3). This increase was not 
likely due to respiratory factors (5, 26) because, as described, we actively controlled 
respiration during the collection of these data. Second, Vomiters also had increases in the 
slope of the hypotensive carotid-cardiac baroreflex after flight, a change that is believed 
to reflect increased vagal control over the sinus node (11). This second finding might 
help explain why the carotid-cardiac baroreflex slope is not significantly decreased in an 
entire group of returning astronauts until 2-4 days after landing (11), when severe motion 

Schlegel et al.. Orthostatic Intolerance After Parabolic Flight 2 1 

sickness in some of the crewmembers is presumably no longer a factor. Third, 
immediately after flight in the seated position in the aircraft, Vomiters had temporally 
prolonged MBP responses during Valsalva phase 11^ (Table 4). Temporal prolongation of 
phase lie ^Iso occurs when seated Valsalva maneuvers are performed during parabolic 
microgravity (48) — i.e., when efferent cardiovagal influences on HR are presumably 
increased (35, 48). 

The finding of increased R-R interval variability after emesis is not inconsistent 
with reports of decreased (10, 19) or unchanged (36) heart rate variability in previous 
human studies during the development of motion sickness because, in those studies, 
changes in heart rate variability were not studied in the context of actual vomiting. On 
the other hand, increased R-R interval variability after emesis is consistent with the 
increased "coefficient of variance of R-R intervals" observed in squirrel monkeys taken 
all the way to vomiting during a visual-vestibular stimulus (20). It may be, therefore, that 
the directional change in the variability of R-R intervals during motion sickness depends 
in part upon the degree of motion sickness attained, with prodromal symptoms (including 
moderate nausea) associated with decreased R-R interval variability (or with unchanged 
R-R interval variability when nausea-related respiratory alterations (2) are experimentally 
negated (36)) and the actual emetic and post-emetic periods associated with increased R- 
R interval variability. Taken together, these findings suggest that if a cardiac "stress 
response" independent of respiratory changes occurs during the development of motion 
sickness (19, 32) (it may not (36)), it is nonetheless superseded by increased fluctuafions 
in vagal-cardiac nerve traffic during and/or after emesis itself, a situation that might be 
roughly paralleled during tilt testing when the acute development of vasovagal 

Schlegel et al., Orthostatic Intolerance After Parabolic Flight 22 

presyncope is accompanied by increases in both the respiratory and non-respiratory 
fluctuations of R-R intervals (37). 

B. Non-Vomiters. The relative increases in the low frequency power of SBP and 
DBP and in the sympathovagal index in non-Vomiters postflight (Table 3) were 
especially evident in the three non-Vomiters who developed frank orthostatic intolerance 
(Fig. 6). The supine autonomic changes in these three individuals were therefore again 
the most reminiscent of clinical POTS (39). However, unlike patients with clinical 
POTS, who have attenuated MBP responses during supine Valsalva phase 11, (47, 49, 50), 
the subjects with POTS-like intolerance in this study had, like astronauts returning from 
space flight (12), accentuated MBP responses during this same Valsalva phase (Fig. 6). 
Two factors might explain this apparent discrepancy. First, clinical POTS is a 
heterogenous disorder, and most patients with POTS do in fact have accentuated MBP 
responses during supine Valsalva phase 11, (P. A. Low, personal communication). Second, 
NASA investigators, including ourselves, typically calculate the magnitude of Valsalva 
phase Il| by using the delta MBP between the trough value in phase 11^ and the peak value 
in phase 11, (12, 13, 48). On the other hand, until recently, most clinicians studying POTS 
have calculated the magnitude of phase 11, as the absolute or percent offset of the BP 
versus the baseline BP obtained prior to the beginning of the maneuver (27, 47, 49, 50). 
It should be noted that in situations where both phase 11^ and phase 11, are determined to 
be accentuated by using the NASA method, the use of the earlier clinical method may 
determine that phase 11, is actually attenuated, depending upon the absolute increment in 
BP during phase I, the absolute decrement in BP during phase 11^, and the absolute 
increment in BP during phase 11,. Therefore, when cross-referencing the results of 

Schlegel et al., Orthostatic Intolerance After Parabolic Flight 23 

studies employing the Valsalva maneuver, these differing historical methods of analyses 
should always be kept in mind. 

Treatment perspectives. In the present study, the varying modes of orthostatic 
failure observed after parabolic flight suggest a slightly less severe version of the 
disparate modes of orthostatic failure recently described by Buckey et al. (6) in astronauts 
after space flight. The differences between the various modes of failure in both studies 
suggest that prophylaxis for orthostatic intolerance in returning crewmembers might best 
be individualized. Currently, NASA requires that all returning astronauts utilize two 
countermeasures against post-spaceflight orthostatic intolerance: G-suit inflation and oral 
fluid and salt loading. However, despite these in-flight countermeasures, up to 64% of 
crewmembers are still unable to complete a 10-min stand test after landing (6). Most 
crewmembers who still experience orthostatic intolerance after landing have postural 
tachycardia in conjunction with either a gradual (6) or immediate (14) failure of the TPR 
response and eventual orthostatic hypotension. Crewmembers who are especially prone 
to this syndrome might therefore benefit from additional late-inflight prophylaxis with a 
peripherally active pressor agent such as Midodrine (27). On the other hand, a non- 
centrally active medication like Midodrine might not be wholly efficacious in 
ameliorating the prostration intolerance of motion sick individuals, whose cardiovascular 
symptoms may be more strictly attributable to upright hyperventilation and cerebral 
vasoconstriction. In these individuals, additional late-inflight prophylaxis with a 
centrally-active antimotion sickness medication, plus or minus Midodrine, might be a 
more useful approach. Although orthostatic hypertension (as in one subject in the present 
study) has not been previously described in returning astronauts, yet other medications 

Schlegel et al., Orthostatic Intolerance After Parabolic Flight 24 

might be useful in preventing/ameliorating that particular syndrome (27). Regardless of 
the specific type of intolerance, a crewmember who becomes lightheaded after landing 
might also be instructed to institute CO2 rebreathing maneuvers (for example, closure of 
his or her launch/re-entry helmet visor if emesis is not imminent), since, if hypocapnia is 
present, such maneuvers will likely improve upright cerebrovascular function (40). 

Limitations. An important limitation to this study was the absence of direct 
measurements of plasma volume. Although deficits in plasma volume correlate poorly 
with deficits in orthostatic tolerance in both returning astronauts (6, 14) and bed rested 
subjects (8), an equivalently poor correlation cannot be assumed to apply a priori to 
parabolic flyers. In addition, we did not measure levels of hormones such as 
catecholamines, arginine vasopressin (AVP), etc., which can be elevated after parabolic 
flight (25). In individuals who vomit as a result of such flight, AVP levels are especially 
elevated (i.e., up to 9-fold after landing) (25). Elevated AVP can in turn enhance arterial 
baroreflex sensitivity (i.e., in certain animal species) (18, 53) and, in humans, it can 
expand intravascular volume (22). 

In summary, we studied orthostatic tolerance and autonomic cardiovascular 
function in 16 healthy test subjects before and after a seated 2-hr parabolic flight. After 
flight, eight of the 16 subjects could not tolerate a 30-min upright tilt test, compared to 
two of the 16 before flight. Of the six newly intolerant subjects, three had vomited as a 
result of parabolic flight (newly intolerant Vomiters) whereas three had not (newly 
intolerant non- Vomiters). After flight, the newly intolerant non-Vomiters (none of whom 
were significantly motion sick) developed a form of orthostatic intolerance resembling 
clinical POTS. This form of intolerance was characterized by an exaggerated 

Schlegel et al.. Orthostatic Intolerance After Parabolic Flight 25 

sympathovagal index in the supine position, an exaggerated hypocapnia and cerebral 
vasoconstriction in the upright position, postural tachycardia, a failure of the upright TPR 
response, and either absolute hypo- or hypertension. On the other hand, the newly 
intolerant Vomiters developed a form of orthostatic intolerance that was not characterized 
by a clear hypotensive or hypertensive event, but rather by comparatively isolated 
hypocapnia and cerebral vasoconstriction during lightheadedness and/or recurrent nausea 
in the upright position. During controlled breathing in the supine position postflight 
compared to preflight, Vomiters also had autonomic changes suggestive of increased 
fluctuations in efferent vagal-cardiac nerve traffic. The most important conclusion from 
this study is that syndromes of orthostatic intolerance resembling those occurring after 
space flight can occur after a brief (i.e., 2-hr) parabolic flight. 

Schlegel et al., Orthostatic Intolerance After Parabolic Flight 26 


The authors thank the test subjects who enthusiastically volunteered for this 
challenging study, Mr. Don Barker for assistance with data collection, Drs. Mike Kassam, 
Jorge Serrador, Paul Dunphy and Paul Picot for assistance with the transcranial Doppler 
and CO2 data, Ms. Ann Sanders for her general assistance, Drs. Alan Feiveson and Dick 
Calkins for statistical assistance, Lynette Bryan, Noel Skinner, Linda Billica and Bob 
Williams for technical assistance inside the aircraft, the Johnson Space Center 
Neurosciences and Cardiovascular Laboratories for help with physiologic measurements, 
and the Johnson Space Center Human Test Subject Facility for the recruitment and care 
of test subjects. 

This research was supported by NASA Grant #199161156 and by a NASA Young 
Investigator Award. 

Address for reprint requests: T.T. Schlegel, NASA Johnson Space Center, Mail Code 
SD3, Houston, TX 77058. 

Schlegel et al., Orthostatic Intolerance After Parabolic Flight 27 


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Transact. Audio Electroacoust. AU-15: 70-73, 1967. 

55. Yates, B. J., and I. A. Kerman. Post-spaceflight orthostatic intolerance: possible 
relationship to microgravity-induced plasticity in the vestibular system. Brain Res. Rev. 
28:73-82, 1998. 

56. Yates, B. J., and A. D. Miller. Physiological evidence that the vestibular system 
participates in autonomic and respiratory control. J. Vestib. Res. 8: 17-25, 1998. 

Schlegel et al., Orthostatic Intolerance After Parabolic Flight 3 1 


Figure 1 . Preflight (light tracing) and postflight (dark tracing) responses to upright tilt in 
a subject (#7, Table 2) who developed frank orthostatic intolerance during his postflight 
tilt test only. The lines within each tracing represent temporal regressions from the end of 
upright tilt back to the second minute of the upright position. CVR^j,,, estimated cerebral 
vascular resistance; MCA-MFV, mean flow velocity of blood in the right middle cerebral 
artery; CO2, nasal end-tidal carbon dioxide level; MBP, mean blood pressure; HR, heart 
rate; SV, stroke volume; TPR, total peripheral resistance. Preflight, this subject 
completed the maximum 30-min of upright tilt in an unremarkable fashion. Postflight, 
however, he developed palpitations and severe lightheadedness, requesting premature 
termination of the tilt test near upright minute 21 (dark vertical line). His postflight signs 
included: 1) progressive postural tachycardia; 2) a gradual failure of the upright TPR 
response; 3) mild relative hypertension; and 4) relative hypocapnia and cerebral 
vasoconstriction with a reversal of the direction (compared to preflight) of the temporal 
regression slopes for CVR^.^,, MCA-MFV and CO2. This subject did not experience 
notable motion sickness either during or after flight. 

Figure 2. Preflight (light tracing) and postflight (dark tracing) responses to upright tilt in 
the lone subject (#5. Table 2) who had postural tachycardia as well as a vasovagal 
episode postflight but who completed an unremarkable tilt test preflight (see Fig. 1 for an 
explanation of abbreviations and temporal regression lines). The Finapres signal was 
unfortunately lost in this subject during postflight upright minutes 0-3.5. Nonetheless, 
her postflight vasovagal episode is clearly shown between the dark vertical lines (near 

Schlegel et al., Orthostatic Intolerance After Parabolic Flight 32 

upright min 22.5), which represent the beginning and end, respectively, of emergent 
downward tilt. Note the abrupt decreases in MBP and HR (as well as the more abrupt 
decreases in TPR, end-tidal COj and MCA-MFV, compared to Fig. 1) that occurred just 
prior to the emergent termination of this subject's postflight tilt test. During upright mins 
5-10 both pre- and postflight (stippled area), this subject also performed metronome- 
controlled breathing at a frequency (0.25 Hz) that was slightly faster than her natural 
respiratory rate. The strong relationship between MCA-MFV and end-tidal COj is 
illustrated by the similar de-trending (i.e., acute lowering) of these two parameters during 
controlled breathing both pre- and postflight. 

Figure 3. Expanded view of min 8-14 only of the postflight response to the upright 
position in a subject (#13, Table 2) who experienced significant nausea and vomiting 
during parabolic flight (see Fig. 1 for an explanation of abbreviations). Although this 
subject was virtually free of motion sickness symptoms in the supine position 35-40 min 
after landing, she redeveloped nausea near upright min 1 1 of the postflight tilt test which 
rapidly progressed to frank retching and vomiting beginning at upright min 12.5. During 
this subject's mild nausea (open bar), prior to her actual emesis, she increased the depth 
of her abdominal respiratory-muscle excursions (bottom) and became relatively 
hypocapnic. At the same time, MCA-MFV decreased while CVR,,, increased. During 
the subject's subsequent upright retching and emesis (shaded bar), exemplified by the 
inordinately large, paroxysmal abdominal respiratory-muscle excursions, a bradycardia 
developed in conjunction with a sharp, transient increase in SV. At the same time, end- 
tidal CO2 and MCA-MFV decreased further while the Finapres-derived parameters 

Schlegel et al., Orthostatic Intolerance After Parabolic Flight 33 

(MBP, TPR and CVR^,,) swung wildly. Although there was no direct evidence for finger- 
cuff-related artifact during minutes 12.5-14 (the subject, leaning forward, used her non- 
cuffed hand to deposit her vomitus into a bag), we could not definitively exclude this 

Figure 4. Preflight (light tracing) and postflight (dark tracing) responses to upright tilt in 
a subject (#3, Table 2) who was orthostatically tolerant both pre- and postflight as well as 
completely resistant to flight- induced motion sickness (see Fig. 1 for an explanation of 
abbreviations and temporal regression lines). The postflight changes experienced by this 
subject in the upright position (i.e., moderate postural tachycardia as well as mild 
hypocapnia and cerebral vasoconstriction relative to preflight) demonstrate that deficits in 
orthostatic tolerance also occurred in so-called "tolerant" subjects. In this individual, 
some of the changes noted postflight may have been related to his more frequent 
respiratory sighing (not shown). 

Figure 5. Postflight tilt-related differences that separated subjects who were tolerant (n = 
8) versus frankly intolerant (n = 8) to the upright position after flight. TPR, total 
peripheral resistance. *P < 0.05 versus tolerant subjects, Mann- Whitney rank sum test. 

Figure 6. Postflight percent changes in measures of supine autonomic cardiovascular 
function in non-Vomiters who did and who did not develop frank intolerance to postflight 
upright tilt, n = 7 (tolerant non-Vomiters) and 3 (intolerant non-Vomiters), respectively. 
*P < 0.05 vs. tolerant non-Vomiters, Mann- Whitney rank sum test. 

Table 1 . Whole group responses to upright tilt 

Preflight Postflight 

Pre flight Postflight 

Preflight Postflight 




PP (mmHg) 

HR (beats/min) 

SV (ml) 


TPR (mmHg/l/min) 

MCA-MFV (cm/s) 

CVRest (mmllg/cm/s) 

ETCO2 (%) 

116 + 2 

127 + 8 

113 + 3 
72 + 2* 
85 + 2* 
131 + 8* 

7.4 + 0.4 8.0 + 0.5* 

12.5 + 0.8 11.3 + 0.8* 

63.5 + 4.8 58.4 + 4.3 

1.7 + 0.2 1.8 + 0.2 

4.6 + 1.4 4.5 + 0.1 



































































111 + 3 
5.8 + 0.4 
16.4 + 1.0 
52.3 + 4.2 
1.6 + 0.2 
4.5 + 0.2 

106 + 3 

76 + 2* 

86 + 2* 

30 + 3 

86 + 4* 

6.6 + 0.5* 

13.7 + 0.8* 

46.8 + 3.7* 
2.0 + 0.3 
4.0 + 

Values are means + SE, SBP, DBP, MBP and PP: systolic, diastolic, mean and pulse blood pressures, respectively; HR, heart rate; .SV, stroke volume; 
CO, cardiac output; TPR, total peripheral resistance; MCA-MFV, middle cerebral artery mean flow velocity; C\R^,. estimated cerebrovascular resistance; 
ET CO3, end-tidal carbon dioxide level, n = 16 except for MCA-MFV and CVR^s,, where « = 15. EfTect of parabolic (light (Wilcoxon signed-rank test): 
*P < 0.05 vs. preflight; t P < 0.01 vs. preflight. 

Table 2. Motion sickness and orthostatic intolerance 

after parabolic flight 



.M.S. score. 

Weight loss 

Frank orthostatic 


overall, then -> 


intolerance during 




postflight tilt?* 






































12 (M) 




16+-> 16+ 



14 (M) 

16-i-> 16+ 








16+-> 6 

Vasovagal § 

Max. = maximum, M.S. = motion sickness, with score defined on the 
basis of Graybiel's 16-point scale (16). Unshaded background, non- 
Vomiters; shaded background, Vomiters. *See text for a discussion of the 
various types of frank postflight orthostatic intolerance. POTS = postural 
tachycardia syndrome. tAlso had vasovagal features, see text. JUpright 
position during the postflight tilt test led to renewed nausea and vomiting 
and therefore to orthostatic intolerance. (jAlso had frank orthostatic 
intolerance pretlight. 

Table 3. Spectral power of supine R-R intervals and arterial pressures pre- and post/light 

Whole Group 
Preflight Postflight 

Vomiters (V) Non-Vomilers (nV) 

Preflight Postflight Preflight Postflight 

Vvs. nV 
Preflight Postflight 

1,91+0,41 3,39+0,57 

3,32+1,06 7,41+3,57 

7,89+1.76 16.65+3.29* 

12.37+3.21 9.68+2.78 

5.29+1.26 4.76+1.28 

Spectral power of R-R intervals 

LFPr.r X 103 1.96+0,25 2,93+0.48 

HFPr.rx103 2.79+0.52 4.12+1.49 

TPr.r X 103 8.62+1.39 10.81 + 1.93 

Spectral power of systolic blood pressures 

LFPsBP II. 70+1.96 17.19+2.71 

HFPsBP 4.93+0.81 3.51+0.56 

TPsBP 61.29+12.11 89.62+12.70* 66.22+28.7 67.63+13.26 

Spectral power of diastolic blood pressures 

LFPdbP 5.97+0.78 8.67+1.45 

HFPdbP 0.92+0.19 1.67+0.80 

TPdbP 19.12+2.61 32.62+4.69t 19.52+2.82 24.41+5.09 

Sympathovagal index 

LFPsBP/HFPR.R 11.11+6.10 26.77+15.50 19.12+16.3 2.29+0.94 

6.03+0.93 5.63+1.41 
1.41+0.39 3.21 + 1.93 

1.99+0.35 2.65+0.69 NS NS 

2.47+0.57 2.14+0.73 NS X 

9.06+2.02 7.31+1.64 NS J 

11.30+2.61 21.69+3.33 NS J 

4.71 + 1.10 2.76+0.34 NS NS 

58.33+10.67 102.81 + 17.89* NS NS 

5.99+1.06 10.02+1.95 NS NS 

0.76+0,18 0,75+0,12 NS NS 

19.52+3,69 35,19+6,61t NS NS 

6.31 + 1,89 41,46+24.01 


Values are means + SE in (msVHz) for R-R interval spectral powers and means + SE in (mmHgVHz) for arterial pressure spectral powers, n = 16 
(whole group), 6 (Vomiters) and 10 (non-Vomiters), respectively. LFP, low frequency power; HFP, high (or respiratory) frequency power; TP, total 
power; SBP, systolic blood pressure; DBP, diastolic blood pressure. Within-group changes (Wilcoxon signed-rank test): *P < 0.05 vs. preflight; fP < 
01 vs. preflight. Between-group changes (Mann-Whitney rank sum test): IP < 0.05; NS, no significant differences noted. 







Table 4. Effect of parabolic flight on responses to Valsalva maneuvers 

Whole Group Vomiters (V) Non-Vomiters (nV) V vs. nV 

Pretlight Postflight Preflight Postflight Preflight Postflight Prejlight Post/light 

Absolute change in MBP during Valsalva phases fig, /// and IV: Supine 

A phase lie -14.78+7.88 -13.40+7.21 -14.65+5.76 -9.39+3.13 -14.88+9.22 -15.80+8.00 

A phase 11) 11.17+5.66 13.25+6.12 11.46+5.98 12.71+3.62 10.99+5.79 13.59+7.41 

AphaselV 20.92+10.11 22.53+7.25 20.02+10.19 18.92+7.03 21.47+10.58 24.70+6.79 

Absolute change in MBP during Valsalva phases IIq, III and IV: Seated 

Aphaselle -22.34+9.99 -18.05+9.88* -23.33+8.46 -15.96+7.47* -21.85+11.08 -19.10+11.11 

Aphaselli 21.39+11.07 15.61+9.63* 15.96+7.96 10.20+7.18* 24.11 + 11.74 18.32+9.85 

AphaselV 25.19+15.36 21.16+12.81 26.16+22.17 23.58+18.36 24.70+12.16 19.97+10.02 

Temporal duration of intrastrain Valsalva phases IIq and III: Supine 

He duration 7.19+1.07 6.78+1.32 6.90+0.84 6.95+1.08 7.36+1.19 6.67+1.49 NS NS 

11] duration 5.64+1.28 5.96+1.35 5.83+1.03 5.89+1.08 5.52+1.44 6.00+1.54 NS NS 

Temporal duration of intrastrain Valsalva phases IIq and II y. Seated 

lie duration 6.12+1.33 6.09+1.34 5.94+1.55 7.26+1.41* 6.21 + 1.28 5.50+0.89 NS t 

111 duration 6.82+1.47 6.29+1.52 6.24+1.33 4.78+1.60 7.11 + 1.52 7.04+0.75 NS NS 

Values are means + SD in mmHg for absolute changes in mean blood pressure (MBP) and means + SD in s for temporal changes in phases 11^ and 11,. 
« = 16 {whole group supine), 6 (Vomiters supine), 10 (non-Vomiters supine or seated), 15 (whole group seated), and 5 (Vomiters .seated), respectively. 
Postflight, seated strains were performed in the aircraft 5 min af\er landing whereas supine strains were performed in the hangar 30-40 min af\er landing. 
Within-group changes (Wilcoxon signed-rank test): *P < 0.05 vs. preflight. Between-group changes (Mann-Whitney rank sum test): iP = 0.02; N,S, no 
significant difTerences noted. 







I f6 / 

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Elapsed Time (min) 



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^ 100 

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Elapsed Time (min) 

ost Pre 


Fl6 3 

Asymptomatic >-Nausea-->-Vomiting-> 

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8 10 12 14 

Elapsed Time in Upright Position (min) 


Fk. H 

O — ' 


Elapsed Time (min) 

Pre, Post 

fi6 ^ 






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Tolerant subjects 
Intolerant subjects 


end vs. early upright 

end upright 

end upright 

end upright 

f 16 


350 ■ 

175 ■ 

10000 • 


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IH Intolerant 






Sympathovagal Index 

120 • 






60 . 













60 . 

30 . 





Valsalva Phase IL 

Valsalva Phase II, 

Baroreflex Range 

Baroreflex Slope